PDGF-CC underlies resistance to VEGF-A inhibition and combinatorial targeting of both suppresses pathological angiogenesis more efficiently
| Autor: | Xiangrong Ren, Yuxiang Du, Qishan Chen, Shuping Zhang, Zhiqin Gao, Lei Zheng, Liying Xing, Rong Ju, Weisi Lu, Yida Jiang, Xianchai Lin, Chen Zhao, Chunsik Lee, Zhimin Ye, Xuri Li, Zhongshu Tang, Delong Huang, Xianglin Li, Shasha Wang, Lijuan Huang, Wei Chen, Jia Mi, Geng Tian, Bin Wang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine Oncology medicine.medical_specialty Angiogenesis VEGF receptors Retinal Pigment Epithelium VEGF-A Mice angiogenesis 03 medical and health sciences Pathological Angiogenesis Internal medicine medicine Animals Humans Cells Cultured Platelet-Derived Growth Factor Lymphokines Mice Inbred C3H drug resistance Neovascularization Pathologic biology Traditional medicine business.industry PDGF-CC Antibodies Neutralizing Choroidal Neovascularization Up-Regulation Mice Inbred C57BL RAW 264.7 Cells 030104 developmental biology Mice Inbred DBA biology.protein Female business Platelet-derived growth factor receptor Signal Transduction Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Lei Zheng 1, 2, * , Chen Zhao 3, * , Yuxiang Du 2 , Xianchai Lin 2 , Yida Jiang 2 , Chunsik Lee 2 , Geng Tian 1 , Jia Mi 1 , Xianglin Li 1 , Qishan Chen 2 , Zhimin Ye 2 , Lijuan Huang 2 , Shasha Wang 2 , Xiangrong Ren 2 , Liying Xing 2 , Wei Chen 2 , Delong Huang 1, 2 , Zhiqin Gao 4 , Shuping Zhang 1 , Weisi Lu 2 , Zhongshu Tang 2 , Bin Wang 5 , Rong Ju 2 , Xuri Li 1, 2 1 Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China 2 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China 3 Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, P. R. China 4 Department of Cell Biology, Weifang Medical University, Weifang, 261053 P. R. China 5 Medical Imaging Institute, Shandong Province Characteristical Key Subject, Medical Imaging and Nuclear Medicine, Binzhou Medical University, Yantai, 264003 P. R. China * Equal first authors Correspondence to: Xuri Li, email: lixr6@mail.sysu.edu.cn Rong Ju, email: jurong@mail.sysu.edu.cn Bin Wang, email: binwang001@aliyun.com Keywords: angiogenesis, PDGF-CC, VEGF-A, drug resistance Received: May 11, 2016 Accepted: October 14, 2016 Published: October 24, 2016 ABSTRACT Anti-VEGF-A therapy has proven to be effective for many neovascular diseases. However, drug resistance to anti-VEGF-A treatment can develop. Also, not all patients with neovascular diseases are responsive to anti-VEGF-A treatment. The mechanisms underlying these important issues remain unclear. In this study, using different model systems, we found that inhibition of VEGF-A directly upregulated PDGF-CC and its receptors in multiple cell types in pathological angiogenesis in vitro and in vivo . Importantly, we further revealed that combinatorial targeting of VEGF-A and PDGF-CC suppressed pathological angiogenesis more efficiently than monotherapy. Given the potent angiogenic activity of PDGF-CC, our findings suggest that the development of resistance to anti-VEGF-A treatment may be caused by the compensatory upregulation of PDGF-CC, and combined inhibition of VEGF-A and PDGF-CC may have therapeutic advantages in treating neovascular diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|